Clinical & Experimental Metastasis

, Volume 22, Issue 1, pp 59–67

Identification of molecular markers for metastasis-related genes in primary breast cancer cells

  • Koshi Mimori
  • Akemi Kataoka
  • Keiji Yoshinaga
  • Mitsuhiko Ohta
  • Yasuaki Sagara
  • Yasuji Yoshikawa
  • Shinji Ohno
  • Graham F. Barnard
  • Masaki Mori
Article

DOI: 10.1007/s10585-005-4417-y

Cite this article as:
Mimori, K., Kataoka, A., Yoshinaga, K. et al. Clin Exp Metastasis (2005) 22: 59. doi:10.1007/s10585-005-4417-y

Abstract

Comparing differential gene expression profiles established by cDNA microarray between normal cells (N), primary carcinoma cells (T), and metastatic carcinoma cells (M) may determine those critical genes directly associated with progression and metastasis of breast cancer. Total RNA was extracted by laser microdissection (LMD) from 20 slices of T, N and M from 6 cases. After amplification by a T7-based system, differentially expressed genes between T, N and M were identified by cDNA microarray. In addition, to clarify the mechanism for altered gene expression, we determined the methylation status by sequencing after bisulfite treatment for intriguing genes. As a result, the expression of motility related protein-1 (MRP-1/CD9), peripheral myelin protein-22 (PMP-22), and caspase 3 (CASP-3) were down-regulated in M compared to T. We focused especially on MRP-1 and found that the expression status of MRP-1 was significantly inversely associated with stage of disease in 56 cases of breast cancer (P<0.05), and the relapse free survival in 5 years was significantly higher in MRP-1 positive cases than those negative cases (P<0.05). Conversely, overexpression, by 11-fold, of signal transduction and translation factors were observed in T compared to N. The cancer specific methylation was observed only in CASP-3 in a case. In conclusion, the establishment of the present assay allows us to detect genes directly associated with each cell population within tumor tissue and gives us clues to identify metastasis-related genes comprehensively in clinical breast cancer cases.

Keywords

cancer specific methylation cDNA microarray, laser microdissection motility related protein-1 relapse free survival 

Abbreviations:

CASP-3

caspase 3

LMD

laser microdissection

MRP-1

motility related protein-1

PMP-22

peripheral myelin protein-22

Copyright information

© Springer 2005

Authors and Affiliations

  • Koshi Mimori
    • 1
  • Akemi Kataoka
    • 2
  • Keiji Yoshinaga
    • 1
  • Mitsuhiko Ohta
    • 1
  • Yasuaki Sagara
    • 2
  • Yasuji Yoshikawa
    • 3
  • Shinji Ohno
    • 2
  • Graham F. Barnard
    • 4
  • Masaki Mori
    • 1
  1. 1.Department of Surgery Medical Institute of BioregulationKyushu UniversityBeppuJapan
  2. 2.Department of SurgeryKyushu National Cancer CenterFukuokaJapan
  3. 3.Pathology, Medical Institute of BioregulationKyushu UniversityBeppuJapan
  4. 4.University of Massachusetts Medical SchoolWorcester, MassachusettsUSA

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